Student Research Committee and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran; Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran; Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Int J Pharm. 2022 Aug 25;624:122027. doi: 10.1016/j.ijpharm.2022.122027. Epub 2022 Jul 16.
Cancer treatments are always associated with various challenges, and scientists are constantly trying to find new therapies and methods. Erlotinib (ELT) is a well-known medicine against non-small cell lung cancer (NSCLC). However, treatments by ELT disrupt therapy due to drug resistance and pose severe challenges to patients. To achieve high-performance treatment, we gained nanostructured lipid carriers (NLCs) to evaluate synergistic anticancer effects of co-delivery of ELT and resveratrol (RES), a natural herbal derived phenol against NSCLC. NLCs are prepared via the hot homogenization method and characterized. In vitro cytotoxicity of formulations were evaluated on adenocarcinoma human alveolar basal epithelial (A549) cells. Prepared NLCs showed a narrow particle size (97.52 ± 17.14 nm), negative zeta potential (-7.67 ± 4.55 mV), and high encapsulation efficiency (EE%) was measured for the prepared co-delivery system (EE% 89.5 ± 5.16 % for ELT and 90.1 ± 6.61 % for RES). In vitro outcomes from cell viability study (12.63 % after 48 h of treatment), apoptosis assay (85.50%.), cell cycle (40.00% arrest in G2-M), and western blotting investigations (decreasing of protein expression levels of survivin, Bcl-2, P-Caspase 3P-caspase 9, and P-ERK 1/2, and additionally, increasing protein levels of BAX, P53, C-Caspase 3 and 9), DAPI staining, and colony formation assays showed the augment cytotoxic performances for co-delivery of ELT and RES loaded NLCs. Our study introduced the co-delivery of ELT and RES by NLCs as a novel strategy to elevate the efficacy of chemotherapeutics for NSCLC.
癌症治疗总是伴随着各种挑战,科学家们一直在努力寻找新的治疗方法和手段。厄洛替尼(ELT)是一种治疗非小细胞肺癌(NSCLC)的知名药物。然而,由于耐药性,ELT 的治疗会中断,这给患者带来了严重的挑战。为了实现高性能的治疗,我们获得了纳米结构脂质载体(NLCs),以评估 ELT 和白藜芦醇(RES)联合给药的协同抗癌作用,RES 是一种天然草药衍生的多酚,可治疗 NSCLC。NLCs 通过热匀化法制备,并进行了特征描述。在腺癌细胞株人肺泡基底上皮细胞(A549)上评估了制剂的体外细胞毒性。制备的 NLCs 表现出窄的粒径(97.52±17.14nm)、负的 Zeta 电位(-7.67±4.55mV)和高包封效率(对于制备的共递送系统,EE%为 89.5±5.16%用于 ELT 和 90.1±6.61%用于 RES)。体外细胞活力研究(处理 48 小时后 12.63%)、细胞凋亡测定(85.50%)、细胞周期(G2-M 期 40.00%阻滞)和 Western blot 研究(存活蛋白、Bcl-2、P-Caspase 3P-caspase 9 和 P-ERK 1/2 的蛋白表达水平降低,另外 BAX、P53、C-Caspase 3 和 9 的蛋白水平升高)、DAPI 染色和集落形成试验显示,ELT 和 RES 负载的 NLC 共递送提高了细胞毒性。我们的研究介绍了通过 NLCs 共递送 ELT 和 RES 作为提高 NSCLC 化疗效果的新策略。